Histone modifications induced by a family of bacterial toxins
Histone modifications induced by a family of bacterial toxins
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DOI：
10.1073/pnas.0702729104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Cossart, Pascale
中科院分区：
文献类型：
--
作者：
Hamon, Melanie Anne;Batsche, Eric;Cossart, Pascale
感染后，病原体重新编程宿主基因表达。在真核细胞中，基因重编程是由转录因子的协同激活/抑制和控制染色质中DNA可及性的各种组蛋白修饰诱导的。我们在这里报告，细菌病原体单核细胞增生李斯特菌诱导组蛋白H3的显着去磷酸化以及组蛋白H4的脱乙酰化在感染的早期阶段。这种作用是由主要的葡萄球菌毒素葡萄球菌溶血素O介导的，不依赖于孔形成。引人注目的是，用相同家族的其他毒素也观察到类似的效果，例如产气荚膜梭菌产气荚膜梭菌溶血素和肺炎链球菌肺炎球菌溶血素。组蛋白修饰水平的降低与宿主基因子集（包括关键免疫基因）的转录活性降低相关。因此，表观遗传调控的控制出现在这里作为一个意想不到的功能共享的几种细菌毒素，突出了一个共同的策略，用于细胞内和细胞外病原体在感染过程中早期调节宿主反应。
Upon infection, pathogens reprogram host gene expression. In eukaryotic cells, genetic reprogramming is induced by the concerted activation/repression of transcription factors and various histone modifications that control DNA accessibility in chromatin. We report here that the bacterial pathogen Listeria monocytogenes induces a dramatic dephosphorylation of histone H3 as well as a deacetylation of histone H4 during early phases of infection. This effect is mediated by the major listerial toxin listeriolysin O in a pore-forming-independent manner. Strikingly, a similar effect also is observed with other toxins of the same family, such as Clostridium perfringens perfringolysin and Streptococcus pneumoniae pneumolysin. The decreased levels of histone modifications correlate with a reduced transcriptional activity of a subset of host genes, including key immunity genes. Thus, control of epigenetic regulation emerges here as an unsuspected function shared by several bacterial toxins, highlighting a common strategy used by intracellular and extracellular pathogens to modulate the host response early during infection.